Bench to bedside: the quest for quality in experimental stroke research - PubMed (original) (raw)

Review

. 2006 Dec;26(12):1465-78.

doi: 10.1038/sj.jcbfm.9600298. Epub 2006 Mar 8.

Affiliations

• PMID: 16525413
• DOI: 10.1038/sj.jcbfm.9600298

Review

Bench to bedside: the quest for quality in experimental stroke research

Ulrich Dirnagl. J Cereb Blood Flow Metab. 2006 Dec.

Abstract

Over the past decades, great progress has been made in clinical as well as experimental stroke research. Disappointingly, however, hundreds of clinical trials testing neuroprotective agents have failed despite efficacy in experimental models. Recently, several systematic reviews have exposed a number of important deficits in the quality of preclinical stroke research. Many of the issues raised in these reviews are not specific to experimental stroke research, but apply to studies of animal models of disease in general. It is the aim of this article to review some quality-related sources of bias with a particular focus on experimental stroke research. Weaknesses discussed include, among others, low statistical power and hence reproducibility, defects in statistical analysis, lack of blinding and randomization, lack of quality-control mechanisms, deficiencies in reporting, and negative publication bias. Although quantitative evidence for quality problems at present is restricted to preclinical stroke research, to spur discussion and in the hope that they will be exposed to meta-analysis in the near future, I have also included some quality-related sources of bias, which have not been systematically studied. Importantly, these may be also relevant to mechanism-driven basic stroke research. I propose that by a number of rather simple measures reproducibility of experimental results, as well as the step from bench to bedside in stroke research may be made more successful. However, the ultimate proof for this has to await successful phase III stroke trials, which were built on basic research conforming to the criteria as put forward in this article.

PubMed Disclaimer

Similar articles

• Emulating multicentre clinical stroke trials: a new paradigm for studying novel interventions in experimental models of stroke.
  Bath PM, Macleod MR, Green AR. Bath PM, et al. Int J Stroke. 2009 Dec;4(6):471-9. doi: 10.1111/j.1747-4949.2009.00386.x. Int J Stroke. 2009. PMID: 19930059
• 1,026 experimental treatments in acute stroke.
  O'Collins VE, Macleod MR, Donnan GA, Horky LL, van der Worp BH, Howells DW. O'Collins VE, et al. Ann Neurol. 2006 Mar;59(3):467-77. doi: 10.1002/ana.20741. Ann Neurol. 2006. PMID: 16453316
• Primer: strengths and weaknesses of meta-analysis.
  Finckh A, Tramèr MR. Finckh A, et al. Nat Clin Pract Rheumatol. 2008 Mar;4(3):146-52. doi: 10.1038/ncprheum0732. Nat Clin Pract Rheumatol. 2008. PMID: 18227829 Review.

Cited by

• The site of embolization related to infarct size, oedema and clinical outcome in a rat stroke model - further translational stroke research.
  Overgaard K, Rasmussen RS, Johansen FF. Overgaard K, et al. Exp Transl Stroke Med. 2010 Sep 17;2(1):17. doi: 10.1186/2040-7378-2-17. Exp Transl Stroke Med. 2010. PMID: 20849633 Free PMC article.
• Impaired alpha(IIb)beta(3) integrin activation and shear-dependent thrombus formation in mice lacking phospholipase D1.
  Elvers M, Stegner D, Hagedorn I, Kleinschnitz C, Braun A, Kuijpers ME, Boesl M, Chen Q, Heemskerk JW, Stoll G, Frohman MA, Nieswandt B. Elvers M, et al. Sci Signal. 2010 Jan 5;3(103):ra1. doi: 10.1126/scisignal.2000551. Sci Signal. 2010. PMID: 20051593 Free PMC article.
• Outcome of experimental stroke in C57Bl/6 and Sv/129 mice assessed by multimodal ultra-high field MRI.
  Pham M, Helluy X, Braeuninger S, Jakob P, Stoll G, Kleinschnitz C, Bendszus M. Pham M, et al. Exp Transl Stroke Med. 2010 Mar 15;2:6. doi: 10.1186/2040-7378-2-6. Exp Transl Stroke Med. 2010. PMID: 20230638 Free PMC article.
• Sustained reperfusion after blockade of glycoprotein-receptor-Ib in focal cerebral ischemia: an MRI study at 17.6 Tesla.
  Pham M, Helluy X, Kleinschnitz C, Kraft P, Bartsch AJ, Jakob P, Nieswandt B, Bendszus M, Stoll G. Pham M, et al. PLoS One. 2011 Apr 1;6(4):e18386. doi: 10.1371/journal.pone.0018386. PLoS One. 2011. PMID: 21483769 Free PMC article.
• Reprint: Good laboratory practice: preventing introduction of bias at the bench.
  Macleod MR, Fisher M, O'Collins V, Sena ES, Dirnagl U, Bath PM, Buchan A, van der Worp HB, Traystman RJ, Minematsu K, Donnan GA, Howells DW. Macleod MR, et al. J Cereb Blood Flow Metab. 2009 Feb;29(2):221-3. doi: 10.1038/jcbfm.2008.101. Epub 2008 Sep 17. J Cereb Blood Flow Metab. 2009. PMID: 18797473 Free PMC article. Review.

Publication types

MeSH terms

LinkOut - more resources

• Full Text Sources

  • Atypon

• Other Literature Sources

  • The Lens - Patent Citations Database

• Medical

  • MedlinePlus Health Information

• Miscellaneous

  • NCI CPTAC Assay Portal